During this investigation, a model of tourniquet-induced forearm ischaemia-reperfusion injury is employed to investigate the role of leucocytes in damage to the vascular endothelium during ischaemia-reperfusion injury. Leucocyte entrapment is investigated by measuring the concentration of leucocytes in venous blood leaving the arm. Neutrophil and monocyte leucocyte subpopulations are isolated by density gradient centrifugation techniques. Cell surface expression of CD11b and the intracellular production of hydrogen peroxide are measured via flow cytometry. Plasma concentrations of elastase and von Willebrand factor (vWF) are measured using enzyme-linked immunosorbemt assay (ELISA) techniques. During ischaemia-reperfusion, there was an increase in CD11b cell surface expression on neutrophils (P=0.040) and monocytes (P=0.049), and a decrease in peripheral blood leucocytes (P=0.019). There was an increase in the intracellular production of hydrogen peroxide by leucocyte subpopulations (P=0.027 [neutrophils], P=0.091 [monocytes]) and in the plasma elastase concentration (P=0.05). There was also a trend to increasing plasma concentration of vWF (P=0.0562), which was measured as a marker of endothelial damage. Ischaemia-reperfusion results in increased adhesiveness, entrapment and activation of leucocytes. Even following a mild ischaemic insult, this leucocyte response was followed immediately by evidence of endothelial damage. These results may have important implications for understanding the development of chronic diseases that involve mild ischaemic episodes.

Background: Monocytes and neutrophils are examples of phagocytic leukocytes, with neutrophils being considered as the 'chief' phagocytic leukocyte. Both monocytes and neutrophils have been implicated to play a key role in the development of ischaemia-reperfusion injury, where they are intrinsically involved in leukocyte-endothelial cell interactions. In this pilot study we hypothesised that mild episodes of tourniquet induced forearm ischaemia-reperfusion injury results in leukocyte activation and changes in inflammatory and coagulation markers.

BackgroundWith an aging society and raised expectations, joint replacement surgery is likely to increase significantly in the future. The development of postoperative complications following joint replacement surgery (for example, infection, systemic inflammatory response syndrome and deep vein thrombosis) is also likely to increase. Despite considerable progress in orthopaedic surgery, comparing a range of biological markers with the ultimate aim of monitoring or predicting postoperative complications has not yet been extensively researched. The aim of this clinical pilot study was to test the hypothesis that lower limb orthopaedic surgery results in changes to coagulation, non-specific markers of inflammation (primary objective) and selective clinical outcome measures (secondary objective).MethodsTest subjects were scheduled for elective total hip replacement (THR) or total knee replacement (TKR) orthopaedic surgery due to osteoarthritis (n = 10). Platelet counts and D-dimer concentrations were measured to assess any changes to coagulation function. C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) were measured as markers of non-specific inflammation. Patients were monitored regularly to assess for any signs of postoperative complications, including blood transfusions, oedema (knee swelling), wound infection, pain and fever.ResultsTHR and TKR orthopaedic surgery resulted in similar changes of coagulation and non-specific inflammatory biomarkers, suggestive of increased coagulation and inflammatory reactions postoperatively. Specifically, THR and TKR surgery resulted in an increase in platelet (P = 0.013, THR) and D-dimer (P = 0.009, TKR) concentrations. Evidence of increased inflammation was demonstrated by an increase in CRP and ESR (P ≤ 0.05, THR and TKR). Four patients received blood transfusions (two THR and two TKR patients), with maximal oedema, pain and aural temperatures peaking between days 1 and 3 postoperatively, for both THR and TKR surgery. None of the patients developed postoperative infections.ConclusionsThe most noticeable changes in biological markers occur during days 1 to 3 postoperatively for both THR and TKR surgery, and these may have an effect on such postoperative clinical outcomes as oedema, pyrexia and pain. This study may assist in understanding the postoperative course following lower limb orthopaedic surgery, and may help clinicians in planning postoperative management and patient care.